Understanding the biophysical basis of energy storage in adipocyte lipid droplets and the metabolic consequences of the failure of this process

This study is based on the hypothesis that humans evolved in a nutritionally challenging environment and have adapted to ensure they have sufficient food and energy intake but have not adapted to having sustained access to high calorie foods. The failure to optimally store surplus energy as fat within lipid droplets in fat cells (adipocytes), results in fat accumulation in other tissues where it causes metabolic diseases, such as type 2 diabetes, fatty liver and cardiovascular disease.

We will study people with lipodystrophy, a rare disorder that is characterised by a lack of body fat. Paradoxically, lipodystrophy leads to severe manifestations of the same metabolic problems associated with obesity. We think that this is a result of a mismatch between the need and capacity to store surplus energy in adipocytes in both cases. This mismatch is extreme in lipodystrophy, which makes it a useful model in which to study the origins of the problem. We have made important genetic discoveries and will now address fundamental biological questions which have emerged from our work.

Our findings will advance our understanding of the molecular basis of fat storage within lipid droplets and the physiological consequences of overload or failure of this process.